The genetic mapping of a locus, termed Lps, that controls the responses of a variety of murine cell types to bacterial lipopolysaccharide (LPS) has been accomplished. Lps is located between the Mup-l and Ps loci on chromosome 4. We propose to examine three aspects of the expression of Lps in C3H/HeJ mice. First, we will determine whether the mitogenic response of B lymphocytes to polyribonucleotides is also controlled by the Lps locus. Second, we will determine whether there exists a specific membrane receptor that binds LPS on the cell surface. This receptor may be defective in C3H/HeJ cells, and may be the product of the Lps locus. Third, we will examine changes in cyclic nucleotide metabolism that may result from the interaction of LPS with a surface receptor. This will involve assaying aderylate and guarylate cyclases, as well as changes in protein kinase activities. BIBLIOGRAPHIC REFERENCES: Watson, J. Differentiation of B. Lymphocytes in C3H/HeJ Mice: The Induction of Ia Antigens by Lipopolysaccharide. J. Immunology 118:1103-1108. (1977). Watson, J., Riblet, R. and Taylor, B. The Response to Lipopolysaccharides in Recombinant Inbred Lines of Mice. J. Expt. Med. (In press) (1977).